IL-18 directs autoreactive T cells and promotes autodestruction in the central nervous system via induction of IFN-γ by NK cells

F. D. Shi, K. Takeda, S. Akira, N. Sarvetnick, H. G. Ljunggren

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Abstract

IL-18 promotes NK cell and Th1 cell activity and may bridge innate and adaptive immune responses. Myelin oligodendrocytes glycoprotein (MOG) is a myelin component of the CNS and is a candidate autoantigen in multiple sclerosis. In the present study we show that IL-18-deficient (IL-18(-/-)) mice are defective in mounting autoreactive Th1 and autoantibody responses and are resistant to MOG35-55 peptide-induced autoimmune encephalomyelitis. IL-18 administration enhances the disease severity in wild-type mice and restores the ability to generate Th1 response in the IL-18(-/-) mice. This restoration was abrogated in NK cell-depleted mice, indicating that the action of IL-18 in promoting the generation of MOG-specific Th cells was dependent on NK cells. Furthermore, transfer of NK cells from recombinase-activating gene 1(-/-) mice, but not from recombinase-activating gene 1/IFN-γ(-/-) mice, rescued the defective Th1 responses in IL-18(-/-) mice and rendered IL-18(-/-) mice susceptible to the induction of autoimmune encephalomyelitis. Thus, IL-18 can direct autoreactive T cells and promote autodestruction in the CNS at least in part via induction of IFN-γ by NK cells.

Original languageEnglish (US)
Pages (from-to)3099-3104
Number of pages6
JournalJournal of Immunology
Volume165
Issue number6
StatePublished - Sep 15 2000

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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